The long-term viability and function of pancreatic islets transplanted as nonvascularized dispersed grafts has not been well established. We report maintenance of nondiabetic carbohydrate metabolism for up to 36 months (17.8 +/- 1.4 months) in 77% of 40 consecutive canine recipients of nonpurified islet grafts transplanted to the spleen by venous reflux. Spontaneous loss of graft function occurred in 9 dogs during the follow-up period. Failure usually occurred within 1 year of implantation and was predicted by low K value and low insulin output on intravenous glucose tolerance tests 1 and 3 months postimplant. High K values and insulin output correlated strongly with maintenance of function beyond 24 months. A sufficient mass of implanted islets can provide satisfactory metabolic control for prolonged periods.